The extracellular adenosine receptor has a modulatory role in the nervous, circulatory, endocrine, and immunological systems. The prospect of harnessing these effects specifically for therapeutic purposes is attractive. A functionalized congener approach to drug design has been applied to the adenosine receptor to produce analogs of agonists and antagonists which have promise as therapeutic agents and as receptor probes. Prodrugs of adenosine agonists and antagonists targeted for the brain and kidneys are being designed. In the antagonist series new analogs which combine potency, water solubility, and A(1)-adenosine receptor selectivity in the same compound are now being evaluated in in vivo testing.